pH Gradient Drives Redox Reactions in the Nucleolar Caps to Modulate Nucleolar Integrity and Function
Description
While enzymatic catalysis is the main driver of redox processes in cells, biomolecular condensates exhibit unique electrochemical properties that can potentiate redox reactions. Nevertheless, the regulatory mechanisms governing the electrochemical equilibrium of biomolecular condensates and their influence on the emergent physicochemical functions remain poorly understood. Here, we demonstrate that specific nucleolar stressors induce alkaline nucleolar caps, which generate an interfacial pH gradient that drives spontaneous redox reactions. Non-enzymatic reactive oxygen species (ROS) production depends on positively charged constituents within the nucleolar caps and correlates strongly with the pH microenvironment. Excessive ROS directly modulates the partition and diffusion of proteins rich in redox-sensitive residues, whereas scavenging ROS markedly accelerates the recovery of nucleolar multiphase organization and functionality upon stress removal. Collectively, our findings propose a non-enzymatic redox mechanism operating within cellular condensates and highlight the critical role of physical interfaces in orchestrating the chemical dynamics of biomolecular condensates.